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1.
J Obstet Gynaecol Res ; 48(11): 2830-2838, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35882511

RESUMO

AIM: To study the effect of Ninjin'yoeito (NYT) on postpartum anemia and on the development of postpartum depression (PPD). METHODS: In this prospective, single-center, open-label, quasi-randomized controlled trial, patients with anemia 1-2 days postdelivery were randomized to receive either NYT or an oral iron preparation for 4 weeks. The primary endpoint was the hemoglobin (Hb) level. Secondary endpoints were fatigue (assessed by the numerical rating scale [NRS]) and prevalence of postpartum depressive symptoms, as defined by an Edinburgh postnatal depression scale (EPDS) score ≥9. Hb levels and fatigue were measured before, and 4 weeks after, treatment and the EPDS was measured 4 weeks posttreatment. RESULTS: Of 1066 participants (NYT group: 532, iron group: 534) 1061 (NYT group: 529, iron group: 532) underwent full analysis. The Hb level increased significantly in both groups (p < 0.001), and there were no significant differences between the groups in terms of the change in Hb levels (NYT: 2.4 ± 0.8 g/dL vs. iron: 2.5 ± 0.7 g/dL, p = 0.098). Fatigue decreased significantly in the NYT group (p < 0.001) but did not change in the iron group, and the difference was significant (p < 0.001). There was a significant difference between the two groups in terms of the prevalence of postpartum depressive symptoms (NYT: 5.7% vs. iron: 9.4%, odds ratio [OR] = 0.58, 95% confidence interval [CI] = 0.36-0.93). CONCLUSION: The results suggest that NYT improves postpartum anemia and fatigue, and may be able to prevent the development of PPD.


Assuntos
Anemia , Depressão Pós-Parto , Feminino , Humanos , Depressão Pós-Parto/diagnóstico , Estudos Prospectivos , Período Pós-Parto , Fadiga , Ferro
2.
Vaccine ; 40(24): 3330-3337, 2022 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-35501179

RESUMO

BACKGROUND: Enterovirus 71 (EV71) is a major cause of outbreaks of hand, foot and mouth disease, most frequently in children, and is a public health concern in the Asia-Pacific region. Takeda is developing TAK-021, an inactivated EV71 vaccine candidate based on sub-genogroup B2 strain MS87. In a phase I clinical trial, TAK-021 was safe, well tolerated, and immunogenic in healthy adults and elicited cross-neutralizing antibodies against heterologous EV71 sub-genogroup viruses. TAK-021 confers protection from lethal challenge with a mouse-adapted homologous strain in AG129 mice. However, it has not been determined whether TAK-021 can provide cross-protection against heterologous EV71 sub-genogroups. METHODS: We examined the efficacy of TAK-021 against challenge with EV71 sub-genogroups B4, B5, C1, C2, and C4 on day 42 (short-term) and sub-genogroups B5 and C4 on day 120 (long-term) after immunization of human scavenger receptor B2 transgenic (hSCARB2-tg) mice with TAK-021 on days 0 and 28. Antibody titers were monitored over 120 days using plaque reduction neutralization test of the homologous vaccine virus. RESULTS: TAK-021 elicited neutralizing antibody (nAb) in greater than 90% of the mice and nAb persisted through day 120. Challenge of control animals led to weight loss and death, as well as virus detection in various organs and histopathological lesions in the brain. All mice that received two doses of TAK-021 developed nAb and survived a short-term challenge given on day 42, while more than 80% survived a long-term challenge given on day 120. EV71 was detected less frequently and at lower levels in organs of immunized mice compared to non-immunized control mice. CONCLUSIONS: The results show that TAK-021 can confer protection in mice against the EV71 sub-genogroups tested.


Assuntos
Enterovirus Humano A , Infecções por Enterovirus , Enterovirus , Vacinas Virais , Animais , Anticorpos Neutralizantes , Anticorpos Antivirais , Enterovirus Humano A/genética , Genótipo , Humanos , Camundongos , Camundongos Transgênicos , Receptores Depuradores , Vacinas de Produtos Inativados
3.
Eur J Pharmacol ; 476(3): 239-47, 2003 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-12969771

RESUMO

TAK-427 (2-[6-[[3-[4-(diphenylmethoxy)piperidino]propyl]amino]imidazo[1,2-b]pyridazin-2-yl]-2-methylpropionic acid dihydrate) is a novel anti-allergic agent that has both histamine H1-receptor antagonist and anti-inflammatory activities. In this study, we evaluated the efficacy of TAK-427 on acute nasal responses and nasal obstruction using various guinea pig models of allergic rhinitis. TAK-427 inhibited the histamine-induced nasal reactions with an ID50 value of 0.633 mg/kg, p.o. TAK-427 (0.1-10 mg/kg, p.o.) and most histamine H1-receptor antagonists tested inhibited the increase in intranasal pressure, nasal hypersecretion, sneezing and nasal itching caused by a single antigen challenge in sensitized guinea pigs. In addition, TAK-427 (0.3, 30 mg/kg, p.o.) significantly inhibited the development of nasal obstruction when sensitized guinea pigs were repeatedly challenged via inhalation with Japanese cedar pollen, whereas the histamine H1-receptor antagonist, azelastine (1 mg/kg, p.o.), and ketotifen (1 mg/kg, p.o.) were without effect. These results suggest that TAK-427 might not only suppress acute nasal symptoms but also ameliorate nasal obstruction via the effects other than those as a histamine H1-receptor antagonist.


Assuntos
Antagonistas dos Receptores Histamínicos H1/farmacologia , Imidazóis/farmacologia , Obstrução Nasal/tratamento farmacológico , Piridazinas/farmacologia , Rinite Alérgica Perene/tratamento farmacológico , Rinite Alérgica Sazonal/tratamento farmacológico , Doença Aguda , Animais , Anti-Inflamatórios/farmacologia , Modelos Animais de Doenças , Cobaias , Histamina/metabolismo , Masculino , Obstrução Nasal/imunologia , Ovalbumina/imunologia , Pólen/imunologia , Rinite Alérgica Perene/imunologia , Rinite Alérgica Perene/fisiopatologia , Rinite Alérgica Sazonal/imunologia , Rinite Alérgica Sazonal/fisiopatologia , Espirro/efeitos dos fármacos , Espirro/imunologia
4.
Chem Pharm Bull (Tokyo) ; 51(2): 122-33, 2003 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-12576644

RESUMO

A series of [1, 2, 4]triazolo[1, 5-b]pyridazines (5) and imidazo[1, 2-b]pyridazines (6) having cyclic amines was synthesized and evaluated for antihistaminic activity and inhibitory effect on eosinophil infiltration. When a piperidine or a piperazine containing a benzhydryl group and a suitable spacer was incorporated at the 6-position, the fused pyridazines were found to exhibit both antihistaminic activity and an inhibitory effect on eosinophil chemotaxis. Above all, 6a showed potent antihistaminic activity, but little blockade of central H(1) receptors in contrast with its complete blockade of peripheral H(1) receptors as determined by an ex vivo binding assay. Furthermore, 6a inhibited eosinophil infiltration of the skin caused by a topical antigen challenge in sensitized guinea pigs, while an antihistamine terfenadine was not effective. After the pharmacokinetic study, 6a was found to be rapidly hydrolyzed to 6o, which was also orally active. Compound 6o, 2-[6-[[3-[4-(diphenylmethoxy)piperidino]propyl]amino]imidazo[1, 2-b]pyridazin-2-yl]-2-methylpropionic acid dihydrate (TAK-427), having both antihistaminic and antiinflammatory activity, is currently undergoing clinical trials as a therapeutic agent for atopic dermatitis and allergic rhinitis.


Assuntos
Eosinófilos/citologia , Eosinófilos/efeitos dos fármacos , Antagonistas dos Receptores Histamínicos H1/síntese química , Antagonistas dos Receptores Histamínicos H1/farmacologia , Animais , Cobaias , Masculino , Traqueia/citologia , Traqueia/efeitos dos fármacos , Traqueia/metabolismo
5.
J Pharmacol Exp Ther ; 303(3): 1283-90, 2002 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12438553

RESUMO

Antigen challenge by patch ovalbumin emulsion induced an eczema-like skin lesion in epicutaneously sensitized guinea pigs. Diseased skin sites were macroscopically characterized by manifestations of dermatitis, such as erythema, edema, and papules, and microscopically characterized by acanthosis, spongiosis, and dermal infiltration by eosinophils. Using such lesions as a model of eczema, we evaluated the potential value of TAK-427 [2-[6-[[3-[4-(diphenylmethoxy)piperidino]propyl]amino] imidazo[1,2-b]pyridazin-2-yl]-2-methylpropionic acid dihydrate] as a therapeutic agent for atopic dermatitis by comparing it with dexamethasone and antihistamines. TAK-427 (0.3-30 mg/kg, p.o.) and dexamethasone (3 and 10 mg/kg, p.o.) inhibited eosinophil infiltration into the skin and ameliorated the dermatitis manifestations and epidermal damage. By contrast, none of the antihistamines tested (azelastine, ketotifen, terfenadine, and cetirizine) suppressed the eosinophil infiltration or dermatitis manifestations. To elucidate the mechanism by which TAK-427 inhibited the development of eczema, we investigated cytokine expression in the affected skin. Both TAK-427 and dexamethasone suppressed the increased mRNA expression of interleukin (IL)-13, granulocyte-macrophage colony-stimulating factor, IL-1alpha, tumor necrosis factor-alpha, interferon-gamma, and IL-8, but not IL-10, suggesting that TAK-427 inhibits allergic inflammation of the skin leading to the development of eczema by inhibiting the expression of proinflammatory cytokines after antigen challenge.


Assuntos
Antialérgicos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Dermatite Alérgica de Contato/tratamento farmacológico , Dermatite Alérgica de Contato/patologia , Modelos Animais de Doenças , Imidazóis/uso terapêutico , Piridazinas/uso terapêutico , Animais , Antialérgicos/farmacologia , Citocinas/biossíntese , Dermatite Alérgica de Contato/metabolismo , Dexametasona/química , Dexametasona/farmacologia , Dexametasona/uso terapêutico , Eczema/tratamento farmacológico , Eczema/metabolismo , Eczema/patologia , Feminino , Cobaias , Antagonistas dos Receptores Histamínicos H1/química , Antagonistas dos Receptores Histamínicos H1/farmacologia , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Imidazóis/química , Imidazóis/farmacologia , Masculino , Piridazinas/química , Piridazinas/farmacologia , RNA Mensageiro/biossíntese
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